Preparation Of 880nm Triggered Nanoparticles For PDT/PTT Combination Therapy Of Tumor

Cancer has become one of the most serious diseases that threaten human health and cause human deaths.Compared with traditional tumor treatment methods,optical therapy has received extensive attention due to its non-invasiveness,convenient operation,non-invasiveness,local selectivity,low drug resistance,and low side effects.Optical therapy mainly includes photothermal therapy(PTT)and photodynamic therapy(PDT),the principle of optical therapy is the photosensitizer is excited by appropriate wavelength light first,and then cause local high temperature or generate reactive oxygen species(ROS)to induce tumor cells apoptosis and/or death.However,after PTT,the remaining tumor cells may still recur due to the heat-resistant properties of the remaining tumor cells.In addition,the ROS generate in the PDT process requires the participation of oxygen molecules in the tumor tissue,so the therapeutic efficiency of PDT is dependent on the concentration of oxygen molecules in the tumor tissue significantly,but hypoxia is a significant feature of solid tumors.Therefore,a single optical treatment mode still has certain limitations.In this study,we focus on the design and preparation of a single near-infrared light triggered high efficiency photosensitizer for PTT/PDT combined therapy of tumor.The specific works are as follows:1.In order to solve low treatment efficiency of single optical treatment mode,herein,an acceptor-donor-acceptor(A-D-A)structure organic small molecule TT-DTC-2N-4Cl was selected as photosensitizer,active targeting ligand folic acid conjugated polyethylene glycol-polybenzyl aspartate(FA-PEG-PBLA)amphiphilic block copolymer was employed to modify the photosensitizer to form a water-soluble nano photosensitizer(PTA-1)for PTT/PDT combination therapy of tumor.The results showed that PTA-1 has a spherical morphology with a diameter of about 213±0.9 nm.After 880 nm laser irradiation,PTA-1 exhibits high photothermal conversion efficiency(42%)and ¹O₂ yield(21.8%,Indocyanine green was selected as control sample),after 5 irradiation/cooling cycles,PTA-1 still exhibits excellent photostability and photothermal and photodynamic behavior.The in vitro cell test results showed that PTA-1 has excellent biocompatibility,and it shows significant phototoxicity against He La cells after 880 nm laser irradiation.2.In order to overcome the effect of hypoxia on PDT therapeutic efficiency,the A-D-A structure organic small molecule 3TT-IC-4Cl was used as the photothermal agent,the oxygen-carrying anthracene endoperoxide(EPO)was selected as the photosensitizer,polyethylene glycol(DSPE-PEG₂₀₀₀)amphiphilic block copolymer was employed to modify the 3TT-IC-4Cl and EPO to form a water-soluble nano photosensitizer(PTA-2)for PTT/PDT combination therapy of tumor.The results showed the diameter of PTA-2 is about 233.8 nm.After 880 nm laser irradiation,PTA-2 exhibits high photothermal conversion efficiency(30.96%)and ¹O₂ yield,after 5 irradiation/cooling cycles,PTA-2 still exhibits excellent photostability and photothermal and photodynamic behavior.The in vitro cell test results showed that PTA-2 has excellent biocompatibility,and it shows significant phototoxicity against He La cells after 880 nm laser irradiation.